Core 2 is essential for the delivery of optimal veterinary care and facilities utilized for the conduct of in vivo experimentation. The Pl.'s of this program project will have access to the Division of Comparative Medicine's AAALAC accredited, centrally managed and operated 175,000 sq. ft. of space, located in five buildings at the Institute. Each of the units has been built or extensively renovated in the last eight years. Four of these buildings have three corridor systems and three have specialized bio-containment units for infectious or hazardous chemical experimentation. Barrier facilities for housing specific pathogen free transgenic mouse colonies are also available. These animal facilities provide MIT investigators a controlled environment with the necessary space, equipment, and containment facilities for performing biomedical related research in animals including germ-free work and also ensures personnel safety during the experimental process. The DCM Comparative Pathology Laboratory will also provide the personnel and expertise to perform histological and immunocytochemical analysis of animal tissues delivered from in vivo studies performed within the framework of the program project. Specifically the role of Core 2 is to provide facilities, equipment, and personnel with expertise to centrally manage and supervise animal husbandry and experimental animal manipulations and provide histopathologic and transgenic services involved in studies conducted in the Program Project Grant. The specific aims are as follows: Specific Aim #1 To provide histology, immunohistochemistry, pathology and molecular characterization expertise for extensive phenotyping and assessment of pathological damage of mouse models used in this program Specific Aim #2 To rederive transgenic and other specialized mouse strains by embryo transfer to assure specific pathogen free status of GEM used in this program Specific Aim #3 Provide colony management of mouse models for use by program project Pi's and as needed generate transgenic animals by pronuclear microinjection of DMAconstructs, embryonic stem cell manipulation, or gene silencing using RNAi technology.